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CASE BASED REVIEW
Ahead of print publication  

Recurrent bilateral idiopathic anterior uveitis with vitritis post Coronavirus Disease 2019 infection


1 Department of Uvea and Ocular Immunology, Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India
2 Department of Medicine, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
3 Department of Rheumatology, Manipal Hospitals, Bengaluru, Karnataka, India
4 Department of Neuro-ophthalmology, Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India

Date of Submission05-Jun-2021
Date of Acceptance13-Jun-2021
Date of Web Publication28-Oct-2021

Correspondence Address:
Srinivasan Sanjay,
Narayana Nethralaya, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_114_21

  Abstract 


A 35-year-old Asian Indian female developed recurrent attacks of bilateral anterior uveitis with vitritis following a febrile episode. Extensive systemic investigations for a febrile episode did not yield any clue. Systemic clinical examination was also within normal limits. In this patient, we found an association of high coronavirus disease 2019 (COVID-19) total antibodies. The polymerase chain reaction for COVID-19 was negative ruling out an active COVID-19 infection. After initiation of oral steroids and immunosuppression the ocular inflammation is now under remission. This report illustrates that the presence of COVID-19 antibodies may presumably play a role in triggering the immune system, this can cause recurrent ocular inflammation in absence of other extraocular inflammation.

Keywords: Anterior uveitis, coronavirus disease-2019, coronavirus disease-2019 antibodies, immunosuppression, ophthalmic manifestations, oral steroids



How to cite this URL:
Sanjay S, Singh YP, Roy D, Mahendradas P, Kawali A, Shetty R. Recurrent bilateral idiopathic anterior uveitis with vitritis post Coronavirus Disease 2019 infection. Indian J Rheumatol [Epub ahead of print] [cited 2021 Dec 9]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=329485




  Introduction Top


Although initial ophthalmic manifestations associated with coronavirus disease 2019 (COVID-19) infection were conjunctival involvement, presently, we have more patients reported with posterior segment manifestations including cotton wool spots, retinal hemorrhages, retinal artery/vein occlusion, ophthalmic artery occlusion, panuveitis, papillophlebitis, multifocal chorioretinitis, bilateral retinitis with retinal vascular occlusions, central serous retinopathy, and Adie's syndrome.[1],[2]

We herein describe a case of bilateral recurrent anterior uveitis associated with high COVID-19 (IgM/IgG) antibodies which persisted even at the time of ocular presentation to us, 9 months after the systemic febrile episode.


  Case Report Top


A 35-year-old Asian Indian female presented to us with unilateral redness, pain, glare, and discomfort in her right eye (OD) of 1-day duration in January 2021. She had a similar presentation in her left eye (OS) about a month earlier and was on tapering dose of topical steroid drops in that eye. OD had a similar episode a month earlier, and she had finished a course of topical steroids 3 weeks before this presentation. She had multiple episodes of ocular inflammation in either eye over the past 14 months and had been treated only with topical steroids elsewhere.

On ocular examination, her best-corrected visual acuity in the OD and OS were 20/25 and 20/40, respectively. Her intraocular pressures in OD and OS were 13 and 18 mmHg, respectively. OD examination showed circumciliary congestion of the conjunctiva, the absence of keratic precipitates in the cornea, anterior chamber showed a flare 2+, cells 2+ with anterior vitreous cells 1+. OS showed flare with no cells in the anterior chamber with anterior vitreous cells 2+. Both eyes fundus examination was within normal limits.

Systemic evaluation and investigations done elsewhere are as illustrated in [Table 1] were all negative except for raised coronavirus antibody (COVID-19) (IgG) titer. All possible systemic autoimmune causes, malignancy, and infective etiology, corroborating with her febrile episode in March 2020 were ruled out.
Table 1: Investigations done for the patient

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In lieu of her recurrent inflammation in both eyes, she was started on topical prednisolone acetate 1% eye drop with homatropine 2% eye drop in the OD with oral steroids (Prednisolone 35 mg - 0.5mg/kg/day) along with oral methotrexate (15 mg per week) in consultation with the rheumatologist. At subsequent follow-ups (next 4 months), steroids were gradually tapered, and the dose of oral methotrexate was gradually increased to 25 mg/week. She responded well and has had no further flares in subsequent months and is currently on oral methotrexate 25 mg/week.


  Discussion Top


We have a 35-year-old Asian Indian female with recurrent ocular inflammatory episodes post-COVID-19 infection, with other systemic evaluation and investigations being negative. COVID reverse transcriptase-polymerase chain reaction (RT-PCR) was not available for the patient for diagnosis of COVID-19 infection; however, IgG antibodies (done twice, once in March 2020 and another in January 2021) in our patient was positive and they have a sensitivity of 99% in detecting past infection). RT-PCR for COVID-19 in January 2021 was negative.[3]

There are many ophthalmic manifestations which may occur after recovery from COVID-19 infections. We had described bilateral pan-uveitis, papillitis, and with central retinal artery occlusion in the OD after recovery from COVID-19 infection possibly due to an immune-mediated event.[4]

Even recently, we have described a patient with unilateral anterior uveitis, which was quiescent for 13 years and reactivated post-COVID-19 infection with no systemic clue.[5]

Bettach et al.[6] described a female patient with bilateral anterior uveitis as a part of multisystem inflammatory syndrome post-COVID-19 infection. Their patient also had only COVID-19 IgG antibodies and negative RT-PCR similar to our patient. Systemically, she had been treated with corticosteroids, vasopressors, and antibiotics for her COVID-19 infection. For her ocular involvement, she had been treated with topical dexamethasone and cycloplegic drops. The difference, however was, our patient developed recurrent attacks of uveitis post-COVID-19.

Another report of a female patient presenting with bilateral redness was diagnosed with bilateral follicular conjunctivitis and suspected viral anterior uveitis; she was later found to be positive for severe acute respiratory syndrome (SARS)-CoV-2 has been described. This patient received topical tropicamide, steroid-antibiotic combination, and other antiseptic eye drops.[7]

COVID-19 infection is associated with dysregulated immune response, perpetual inflammation, and development of de novo autoantibodies.[8]

The human body has both innate and the adaptive immune response in recognizing and eliminating foreign pathogens. Clinical patterns, disease severity, and progression post-COVID-19 may differ based on the suboptimal or unrestrained immune response.[9]

Identification of specific immune signatures may provide novel insights into the divergent disease trajectories observed in individual patients and aid the design of more targeted therapeutic approaches.[10],[11],[12] Complement system probably also plays a part of the immune response post-COVID-19 infection. Unrestrained complement activation can be detrimental to different organs.[13],[14] Complement C3a (proinflammatory peptide) and C5a (potent anaphylatoxin). C5b (membrane attack complex) is responsible for the terminal event of complement activation.[13]

There are reports of autoimmune hemolytic anemia, systemic lupus erythematosus, and rheumatoid arthritis post-COVID-19 infection.[8],[15] Rodriguez et al. proposed the development of a “crossroad” of autoimmunity/autoinflammation related to the pathogenesis of COVID-19.[8]

Post-COVID-19 patients may mimic other hyperinflammatory states such as SARS, acute respiratory disease syndrome, cytokine storm syndrome, and post-ICU syndrome. These conditions may lead to a chronic state of accelerated state of chronic subclinical systemic inflammation often seen in aging (termed inflammaging), resulting in increased and worsening age-related conditions including frailty even in younger individuals both in short and long term.[16] Accelerated inflammaging, loss of immune tolerance, delayed interferon response, molecular mimicry, transient suppression of regulatory T cells, and loss of “sentinel effect” of innate immunity might all contribute to inappropriate immune reconstitution post-COVID-19.[17]

In conclusion, we describe a patient with bilateral recurrent ocular inflammatory disease following COVID-19. Our patient achieved remission after starting oral steroids and immunosuppression. Ocular inflammatory syndrome is a distinct possibility after COVID-19 infection, which can be diagnosed after ruling out other systemic causes. Patient's uveitis started before the onset of pandemic in India. Whether the multiple recurrences were due to the COVID infection or due to delay in starting immunosuppression cannot be proven.

Declaration

The study was approved by the Narayana Nethralaya Ethics committee, Vide approval number EC reference NO C/2020/09/09 (virtual). All tenets of the Helsinki declaration were adhered to.

Patient's written and informed consent was obtained for inclusion in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sanjay S, Gowda PB, Rao B, Mutalik D, Mahendradas P, Kawali A, et al. “Old wine in a new bottle”-Post COVID-19 infection, central serous chorioretinopathy and the steroids. J Ophthalmic Inflamm Infect 2021;11:14.  Back to cited text no. 1
    
2.
Mahendradas P, Hande P, Patil A, Kawali A, Sanjay S, Ahmed SA, et al. Bilateral post fever retinitis with retinal vascular occlusions following severe acute respiratory syndrome corona virus (SARS-CoV2) infection. Ocul Immunol Inflamm. 2021:1-6. doi: 10.1080/09273948.2021.1936564. Epub ahead of print.  Back to cited text no. 2
    
3.
Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev 2020;6:CD013652.  Back to cited text no. 3
    
4.
Sanjay S, Srinivasan P, Jayadev C, Mahendradas P, Gupta A, Kawali A, et al. Post COVID-19 ophthalmic manifestations in an Asian Indian Male. Ocul Immunol Inflamm 2021;18:1-6.  Back to cited text no. 4
    
5.
Sanjay S, Mutalik D, Gowda S, Mahendradas P, Kawali A, Shetty R. “Post Coronavirus Disease (COVID-19) Reactivation of a Quiescent Unilateral Anterior Uveitis”. SN Compr Clin Med. 2021:1-5. doi: 10.1007/s42399-021-00985-2. Epub ahead of print.  Back to cited text no. 5
    
6.
Bettach E, Zadok D, Weill Y, Brosh K, Hanhart J. Bilateral anterior uveitis as a part of a multisystem inflammatory syndrome secondary to COVID-19 infection. J Med Virol 2021;93:139-40.  Back to cited text no. 6
    
7.
Mazzotta C, Giancipoli E. Anterior acute uveitis report in a SARS-CoV-2 patient managed with adjunctive topical antiseptic prophylaxis preventing 2019-nCoV spread through the ocular surface route. Int Med Case Rep J 2020;13:513-20.  Back to cited text no. 7
    
8.
Rodríguez Y, Novelli L, Rojas M, De Santis M, Acosta-Ampudia Y, Monsalve DM, et al. Autoinflammatory and autoimmune conditions at the crossroad of COVID-19. J Autoimmun 2020;114:102506.  Back to cited text no. 8
    
9.
Perico L, Benigni A, Casiraghi F, Ng LF, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol 2021;17:46-64.  Back to cited text no. 9
    
10.
Lucas C, Wong P, Klein J, Castro TB, Silva J, Sundaram M, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020;584:463-9.  Back to cited text no. 10
    
11.
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020;27:992-1000.e3.  Back to cited text no. 11
    
12.
Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020;369:eabc8511.  Back to cited text no. 12
    
13.
Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int 2020;98:314-22.  Back to cited text no. 13
    
14.
Song WC, FitzGerald GA. COVID-19, microangiopathy, hemostatic activation, and complement. J Clin Invest 2020;130:3950-3.  Back to cited text no. 14
    
15.
Perrot L, Hemon M, Busnel JM, Muis-Pistor O, Picard C, Zandotti C, et al. First flare of ACPA-positive rheumatoid arthritis after SARS-CoV-2 infection. Lancet Rheumatol 2021;3:e6-8.  Back to cited text no. 15
    
16.
Bektas A, Schurman SH, Franceschi C, Ferrucci L. A public health perspective of aging: do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term inflammaging? Immun Ageing. 2020;17:23. doi: 10.1186/s12979-020-00196-8.  Back to cited text no. 16
    
17.
Cañas CA. The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals. Med Hypotheses 2020;145:110345.  Back to cited text no. 17
    



 
 
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